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Study of AT-02 in Healthy Volunteers and Subjects With Systemic Amyloidosis (AT02-001)

Primary Purpose

Amyloidosis; Systemic

Status
Recruiting
Phase
Phase 1
Locations
Australia
Study Type
Interventional
Intervention
AT-02
AT-02 (Placebo)
Sponsored by
Attralus, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Amyloidosis; Systemic

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

Eligibility Criteria for Healthy Volunteers:

Healthy volunteers are eligible to be included in the study only if all the following criteria apply:

  1. Understands the study procedures and can give signed informed consent
  2. Male or female between >18 and <56 years of age.
  3. Willing and able to comply with this protocol and informed consent and be available for the entire duration of the study.
  4. Willing to abstain from alcohol and strenuous physical activity (i.e., strenuous or unaccustomed weightlifting, running, bicycling, etc.) from 48 hours prior to study treatment administration until discharge from the clinical unit and prior to each outpatient visit.
  5. In good general health, determined by no clinically significant findings in the opinion of the Investigator from medical history, physical examination, 12-lead electrocardiogram (ECG), clinical laboratory findings, and vital signs at Screening and Phase 1 unit Check-in.
  6. Has body mass index (BMI) of 18 to 32 kg/m2, inclusive.
  7. Women of childbearing potential (WOCBP)

    1. WOCBP must have a negative serum or urine pregnancy test within 24 hours prior to the start of study drug.
    2. Must not be breastfeeding, lactating, or planning a pregnancy during the study period.
    3. WOCBP who are not exclusively in same-sex relationships must agree to remain abstinent (complete avoidance of heterosexual intercourse) or use adequate contraceptive methods, defined as use of a condom by the male partner combined with use of a highly effective method of contraception by the female partner, during the treatment period and for at least 105 days after the last dose of study intervention.
  8. Postmenopausal females:

    a) Postmenopausal females under the age of 55 years must have a documented serum follicle stimulating hormone (FSH) level >40 mIU/mL to confirm menopause

  9. Women of non-childbearing potential (WONCBP) and female participants with vasectomized male partners:

    a) WONCBP must agree to remain abstinent (complete avoidance of intercourse) or the male partners of WONCBP participants must wear a condom to protect against the transfer of study intervention through bodily fluids during the treatment period and for at least 105 days after the last dose of study intervention.

  10. Male participants:

    1. Male participants must inform their female sexual partners who are WOCBP of the contraceptive requirements of the protocol and are expected to adhere to using contraception with their partner.
    2. Male participants with female sexual partners who are WOCBP must agree to remain abstinent (complete avoidance of heterosexual intercourse) or use adequate contraceptive methods, defined as use of a condom by the male partner combined with use of a highly effective method of contraception by the female partner, during the treatment period and for at least 165 days after the last dose of study intervention.
    3. Male participants must not donate sperm for at least 165 days after the last dose of study intervention.
    4. Male participants with potentially postmenopausal partners who are under the age of 55 years must use condoms unless their partner's postmenopausal status has been confirmed by FSH level.
    5. Male participants in same-sex relationships or in relationships with WONCBP must agree to remain abstinent (complete avoidance of intercourse) or use a condom to prevent exposure of the partner to study intervention through ejaculate/seminal fluid during the treatment period and for at least 165 days after the last dose of study intervention.

Eligibility Criteria for Subjects with Systemic Amyloidosis:

Subjects with systemic amyloidosis are eligible to be included in the study only if all the following criteria apply:

  1. Understands the study procedures and can give signed informed consent
  2. Male or female more than18 years of age.
  3. Has a confirmed diagnosis of AL, ATTR, or other form of systemic amyloidosis, based on any one of the following:

    1. A histologic confirmation with a biopsy containing deposits of apple-green birefringent, Congophilic material or other amyloid staining (i.e., thioflavin T or sulfated alcian blue) with confirmatory immunohistochemistry, mass spectrometry or identification of an amyloidogenic genetic variant;
    2. Genetic screening with presence of amyloid-related pathology; or
    3. Amyloid-specific imaging study (e.g., bone scintigraphy and echocardiogram/CMR consistent with ATTR cardiac amyloid)
  4. Subjects with AL systemic amyloidosis must have achieved a hematologic very good partial response (VGPR) or complete response (CR) based on their most recent assessment (e.g., difference in free light chains less than 40 mg/L) and within 12 months of Screening and may be receiving maintenance daratumumab.
  5. Subjects with ATTR systemic amyloidosis may be receiving a TTR silencer (e.g., inotersen, vutrisiran, or patisiran) or a stabilizer (e.g., tafamadis or diflunisal), but not both.
  6. Women of childbearing potential (WOCBP):

    1. WOCBP must have a negative serum or urine pregnancy test within 24 hours prior to the start of study drug.
    2. Must not be breastfeeding, lactating, or planning a pregnancy during the study period.
    3. WOCBP who are not exclusively in same-sex relationships must agree to remain abstinent (complete avoidance of heterosexual intercourse) or use adequate contraceptive methods, defined as use of a condom by the male partner combined with use of a highly effective method of contraception by the female partner, during the treatment period and for at least 105 days after the last dose of study intervention.
  7. Postmenopausal females:

    a. Postmenopausal females under the age of 55 years must have a documented serum follicle stimulating hormone (FSH) level >40 mIU/mL to confirm menopause

  8. Women of non-childbearing potential (WONCBP) and female participants with vasectomized male partners:

    a. WONCBP must agree to remain abstinent (complete avoidance of intercourse) or the male partners of WONCBP participants must wear a condom to protect against the transfer of study intervention through bodily fluids during the treatment period and for at least 105 days after the last dose of study intervention.

  9. Male participants:

    1. Male participants must inform their female sexual partners who are WOCBP of the contraceptive requirements of the protocol and are expected to adhere to using contraception with their partner.
    2. Male participants with female sexual partners who are WOCBP must agree to remain abstinent (complete avoidance of heterosexual intercourse) or use adequate contraceptive methods, defined as use of a condom by the male partner combined with use of a highly effective method of contraception by the female partner, during the treatment period and for at least 165 days after the last dose of study intervention.
    3. Male participants must not donate sperm for at least 165 days after the last dose of study intervention.
    4. Male participants with potentially postmenopausal partners who are under the age of 55 years must use condoms unless their partner's postmenopausal status has been confirmed by FSH level.
    5. Male participants in same-sex relationships or in relationships with WONCBP must agree to remain abstinent (complete avoidance of intercourse) or use a condom to prevent exposure of the partner to study intervention through ejaculate/seminal fluid during the treatment period and for at least 165 days after the last dose of study intervention.

Exclusion Criteria:

  • Healthy volunteers are excluded from the study if any of the following criteria apply:

    1. Subject is mentally or legally incapacitated, has a history of psychosis, or has significant emotional problems at the time of the study according to the Investigator.
    2. Subject has a history or presence of significant cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, or neurologic disease according to the Investigator or reported history of HIV infection.
    3. Subject has a history of poorly controlled asthma or a history of anaphylaxis or other significant allergy in the opinion of the Investigator
    4. Subject has a history of any ongoing medical condition requiring treatment with prescription medication within the past two (2) weeks.
    5. Subject's estimated creatinine clearance/glomerular filtration rate (eGFR) using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation is ≤80 mL/min.
    6. Subject has clinically significant abnormalities on pre-study clinical examination or laboratory safety tests. Laboratory safety assessments (e.g., serum chemistry, hematology, coagulation) will be performed at Screening and on Day -1 (if Screening is prior to Day -1) to confirm eligibility. Screening safety labs may be repeated at the Investigator's discretion.
    7. Hemoglobin <12 gm/dL or seropositivity for hepatitis B surface antigen, or hepatitis C antibodies at Screening.
    8. Has received heparin or heparin analogs (e.g., enoxaparin, dalteparin, fondaparinux) within seven (7) days prior to Day 1.
    9. Use of any prescription or OTC medications including food supplements and herbal medications (e.g., St. John's wort), except for contraceptive medications, a daily multivitamin, and/or as needed (prn) acetaminophen/paracetamol (not exceeding 2 grams/day) within seven (7) days prior to study treatment administration.
    10. History of malignancy, except adequately treated basal or squamous cell carcinoma or in situ carcinoma of the uterine cervix.
    11. History of drug allergy or drug hypersensitivity, or intolerance of IV or subcutaneous injections.
    12. Any female who is pregnant or breastfeeding, or any female who is planning to become pregnant during the study and follow-up periods.
    13. Any condition that, in the Investigator's opinion, may compromise study participation, present a safety risk to the subject, or may confound the interpretation of the study results.
    14. A QT duration corrected for heart rate by Fridericia's formula (QTcF) >450 millisecond (msec) based on averaged QTcF values of triplicate ECGs (obtained at 1-minute intervals at Screening).
    15. Subject has had surgery, experienced significant blood loss, or donated a unit of blood within the last 30 days.
    16. Subject has donated a unit of plasma in the last seven (7) days.
    17. Subject has participated in another clinical study within the last four (4) weeks or within five (5) half-lives of the prior study drug, whichever is longer.
  • Subjects with systemic amyloidosis are excluded from the study if any of the following criteria apply:

    1. Is pregnant or breastfeeding.
    2. Is mentally or legally incapacitated, has significant emotional problems at the time of the study, or has a history of psychosis.
    3. Receiving hemodialysis or peritoneal dialysis.
    4. Myocardial infarction within 3 months of Screening.
    5. New York Heart Association Class III or IV heart failure.
    6. Heart failure not predominantly caused by cardiac amyloid.
    7. Any severe uncorrected cardiac valve disease.
    8. Respiratory insufficiency requiring oxygen therapy.
    9. Currently receiving or has received within three (3) months prior to Screening: melphalan, bortezomib, thalidomide, lenalidomide, rituximab, or cyclophosphamide.
    10. Has received heparin or heparin analogs (e.g., enoxaparin, dalteparin, fondaparinux) within seven (7) days prior to administration of AT-02.
    11. Active malignancy with exception of adequately treated basal cell carcinoma, squamous cell carcinoma of the skin, in situ cervical cancer, low risk prostate cancer with Gleason score less than 7 and prostate specific antigen less than 10 mg/mL, any other cancer from which the subject has been disease-free for greater than and equal 2 years.
    12. Uncontrolled or active infection.
    13. Autoimmune disease requiring treatment with immunosuppressive/modulating treatment in the last year.
    14. History of solid organ transplantation or ventricular assist device.
    15. Suspected or known drug or alcohol abuse, serious psychiatric or any other medical condition, which, in the opinion of the Investigator, makes the subject unsuitable.
    16. Has any concurrent illness that, in the opinion of the Investigator, might confound the results of the study or pose additional risk to the subject.
    17. Subject's screening alanine transaminase (ALT) or aspartate transaminase (AST) is greater than 2.5x upper limit of normal (ULN).
    18. Subject's screening NT-proBNP is greater tha equal 6000 pg/mL.
    19. Subject's screening estimated creatinine clearance/eGFR using the CKD-EPI equation is less than 30 mL/min.
    20. Subject is currently participating in an interventional clinical study or has participated in another clinical study within the last four (4) weeks or within five (5) half-lives of the prior study drug, whichever is longer.

Sites / Locations

  • Q-Pharm Pty LtdRecruiting
  • Princess Alexandra HospitalRecruiting
  • Flinders Medical CentreRecruiting
  • Box Hill HospitalRecruiting
  • Royal Perth Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Placebo Comparator

Experimental

Experimental

Arm Label

Part 1 AT-02

Part 1 Placebo

Part 2 AT-02

Part 3 AT-02

Arm Description

Part 1 enrolling Healthy Volunteers (Randomised, Double-blind) Drug: AT-02 Dosage: 30mg to 1000mg Dosage Form & Route of Admin: Solution for IV Infusion

Part 1 enrolling Healthy Volunteers (Randomised, Double-blind) Dosage Form & Route of Admin: Normal Saline Solution for IV Infusion

Part 2 enrolling Systemic Amyloidosis Participants (Single-Arm, Open-label) Drug: AT-02 Dosage: 300mg to 4000mg Frequency: Single Dose Dosage Form & Route of Admin: Solution for IV Infusion

Part 3 enrolling Systemic Amyloidosis Participants (Single-Arm, Open-label) Drug: AT-02 Dosage: Dose levels will be determined by the SRC. The starting dose in Part 3 will be determined by the SRC based on all available safety, tolerability, PK, and PD data from all prior cohorts Frequency: Multiple Doses Dosage Form & Route of Admin: Solution for IV Infusion

Outcomes

Primary Outcome Measures

Incidence and severity of treatment-emergent adverse events (TEAEs) from Day 1 to end of study (EOS).
Safety will be assessed by review of clinical laboratory parameters and incidence and severity of TEAEs (graded using Common Terminology Criteria for Adverse Events (CTCAE) version 5).
Incidence of dose-limiting toxicities (DLTs) in subjects with systemic amyloidosis.
A DLT is defined as any related TEAE with a National Cancer Institute (NCI) CTCAE version 5.0 Grade ≥3 which also represents a shift from Baseline clinical status of >1 NCI CTCAE Grade.
Incidence and frequency of abnormal and clinically significant abnormal clinical laboratory parameter values.
Incidence of treatment-emergent anti-drug antibodies (ADA)
The number and percentage of subjects who develop detectable ADA will be summarized by dose cohort.

Secondary Outcome Measures

To determine the plasma pharmacokinetics (PK) profile of AT-02
Parameter: time to maximum observed AT-02 concentration (Tmax).
To determine the plasma pharmacokinetics (PK) profile of AT-02
Parameter: maximum observed concentration of AT-02 (Cmax).
To determine the plasma pharmacokinetics (PK) profile of AT-02
Parameter: area under the plasma concentration versus time curve (AUC).
To determine the plasma pharmacokinetics (PK) profile of AT-02
Parameter: volume of distribution at steady state (Vss).
To determine the plasma pharmacokinetics (PK) profile of AT-02
Parameter: total body clearance (CL) of AT-02.
To determine the plasma pharmacokinetics (PK) profile of AT-02
Parameter: AT-02 half-life (t1/2).

Full Information

First Posted
August 23, 2022
Last Updated
September 12, 2023
Sponsor
Attralus, Inc.
Collaborators
Novotech (Australia) Pty Limited
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1. Study Identification

Unique Protocol Identification Number
NCT05521022
Brief Title
Study of AT-02 in Healthy Volunteers and Subjects With Systemic Amyloidosis
Acronym
AT02-001
Official Title
A Three-part, Phase 1, Single-ascending, and Multiple-ascending Dose Escalation Study in Healthy Volunteers and Subjects With Systemic Amyloidosis to Assess the Safety, Tolerability, and Pharmacokinetics of AT-02
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
September 1, 2022 (Actual)
Primary Completion Date
March 1, 2024 (Anticipated)
Study Completion Date
March 1, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Attralus, Inc.
Collaborators
Novotech (Australia) Pty Limited

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This is a multicenter, international, three-part, Phase 1 study designed to evaluate the safety, tolerability, and PK of rising single doses of AT-02 in healthy volunteers and in subjects with systemic amyloidosis and to assess the safety, tolerability, and PK of multiple doses of AT-02 in subjects with systemic amyloidosis.
Detailed Description
Systemic amyloidosis is an incurable disease, and about 20% of patients with cardiac or advanced kidney involvement experience early deaths (<1 year). Despite recent progress in proteasome inhibitors, chemotherapies, and immunotherapies that target plasma cells have greatly improved the prognosis of patients with systemic amyloidosis, median survival remains low at approximately five years. AT-02 (INN: not yet available) is a full-length, humanized, recombinant immunoglobulin 1 (IgG1)-like glycoprotein monoclonal antibody (mAb) that is being developed to treat systemic amyloidosis. This is a three-part, Phase 1 study designed to evaluate the safety, tolerability, and PK of rising single doses of AT-02 in healthy volunteers (HV) and in subjects with systemic amyloidosis (SA) and to assess the safety, tolerability, and PK of multiple doses of AT-02 in subjects with systemic amyloidosis. Part 1 is a double-blind, single-center, single-ascending dose escalation study in HV to assess the safety, tolerability, and PK of AT-02. Healthy volunteers between 18 to 56 years of will be enrolled in the Part 1 study. Part 2 is an open-label, single-ascending dose escalation study in subjects with systemic amyloidosis to assess the safety, tolerability, and PK of AT-02 and to identify a maximum tolerated dose (MTD). Subjects with SA over 18 years of age will be involved in the Part 2 study. Part 3 is an open-label, multiple-ascending dose, dose escalation study in subjects with systemic amyloidosis to assess the safety, tolerability, PK, PD, and clinical activity of multiple doses of AT-02. Subjects with SA ≥18 and ≤85 years of age will be involved in the Part 3 study.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Amyloidosis; Systemic

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Masking Description
Double blind (Part 1) Open Label (Part 2) Open Label (Part 3)
Allocation
Randomized
Enrollment
100 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Part 1 AT-02
Arm Type
Experimental
Arm Description
Part 1 enrolling Healthy Volunteers (Randomised, Double-blind) Drug: AT-02 Dosage: 30mg to 1000mg Dosage Form & Route of Admin: Solution for IV Infusion
Arm Title
Part 1 Placebo
Arm Type
Placebo Comparator
Arm Description
Part 1 enrolling Healthy Volunteers (Randomised, Double-blind) Dosage Form & Route of Admin: Normal Saline Solution for IV Infusion
Arm Title
Part 2 AT-02
Arm Type
Experimental
Arm Description
Part 2 enrolling Systemic Amyloidosis Participants (Single-Arm, Open-label) Drug: AT-02 Dosage: 300mg to 4000mg Frequency: Single Dose Dosage Form & Route of Admin: Solution for IV Infusion
Arm Title
Part 3 AT-02
Arm Type
Experimental
Arm Description
Part 3 enrolling Systemic Amyloidosis Participants (Single-Arm, Open-label) Drug: AT-02 Dosage: Dose levels will be determined by the SRC. The starting dose in Part 3 will be determined by the SRC based on all available safety, tolerability, PK, and PD data from all prior cohorts Frequency: Multiple Doses Dosage Form & Route of Admin: Solution for IV Infusion
Intervention Type
Drug
Intervention Name(s)
AT-02
Intervention Description
AT-02 via IV infusion
Intervention Type
Other
Intervention Name(s)
AT-02 (Placebo)
Intervention Description
Normal saline solution via IV infusion
Primary Outcome Measure Information:
Title
Incidence and severity of treatment-emergent adverse events (TEAEs) from Day 1 to end of study (EOS).
Description
Safety will be assessed by review of clinical laboratory parameters and incidence and severity of TEAEs (graded using Common Terminology Criteria for Adverse Events (CTCAE) version 5).
Time Frame
Up to 57+/-7 days
Title
Incidence of dose-limiting toxicities (DLTs) in subjects with systemic amyloidosis.
Description
A DLT is defined as any related TEAE with a National Cancer Institute (NCI) CTCAE version 5.0 Grade ≥3 which also represents a shift from Baseline clinical status of >1 NCI CTCAE Grade.
Time Frame
Up to 85+/-7 Days
Title
Incidence and frequency of abnormal and clinically significant abnormal clinical laboratory parameter values.
Time Frame
Up to 85+/-7 Days
Title
Incidence of treatment-emergent anti-drug antibodies (ADA)
Description
The number and percentage of subjects who develop detectable ADA will be summarized by dose cohort.
Time Frame
Up to 85+/-7 Days
Secondary Outcome Measure Information:
Title
To determine the plasma pharmacokinetics (PK) profile of AT-02
Description
Parameter: time to maximum observed AT-02 concentration (Tmax).
Time Frame
Up to 85+/-7 Days
Title
To determine the plasma pharmacokinetics (PK) profile of AT-02
Description
Parameter: maximum observed concentration of AT-02 (Cmax).
Time Frame
Up to 85+/-7 Days
Title
To determine the plasma pharmacokinetics (PK) profile of AT-02
Description
Parameter: area under the plasma concentration versus time curve (AUC).
Time Frame
Up to 85+/-7 Days
Title
To determine the plasma pharmacokinetics (PK) profile of AT-02
Description
Parameter: volume of distribution at steady state (Vss).
Time Frame
Up to 85+/-7 Days
Title
To determine the plasma pharmacokinetics (PK) profile of AT-02
Description
Parameter: total body clearance (CL) of AT-02.
Time Frame
Up to 85+/-7 Days
Title
To determine the plasma pharmacokinetics (PK) profile of AT-02
Description
Parameter: AT-02 half-life (t1/2).
Time Frame
Up to 85+/-7 Days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Eligibility Criteria for Healthy Volunteers: Healthy volunteers are eligible to be included in the study only if all the following criteria apply: Understands the study procedures and can give signed informed consent Male or female between >18 and <56 years of age. Willing and able to comply with this protocol and informed consent and be available for the entire duration of the study. Willing to abstain from alcohol and strenuous physical activity (i.e., strenuous or unaccustomed weightlifting, running, bicycling, etc.) from 48 hours prior to study treatment administration until discharge from the clinical unit and prior to each outpatient visit. In good general health, determined by no clinically significant findings in the opinion of the Investigator from medical history, physical examination, 12-lead electrocardiogram (ECG), clinical laboratory findings, and vital signs at Screening and Phase 1 unit Check-in. Has body mass index (BMI) of 18 to 32 kg/m2, inclusive. Women of childbearing potential (WOCBP) WOCBP must have a negative serum or urine pregnancy test within 24 hours prior to the start of study drug. Must not be breastfeeding, lactating, or planning a pregnancy during the study period. WOCBP who are not exclusively in same-sex relationships must agree to remain abstinent (complete avoidance of heterosexual intercourse) or use adequate contraceptive methods, defined as use of a condom by the male partner combined with use of a highly effective method of contraception by the female partner, during the treatment period and for at least 105 days after the last dose of study intervention. Postmenopausal females: a) Postmenopausal females under the age of 55 years must have a documented serum follicle stimulating hormone (FSH) level >40 mIU/mL to confirm menopause Women of non-childbearing potential (WONCBP) and female participants with vasectomized male partners: a) WONCBP must agree to remain abstinent (complete avoidance of intercourse) or the male partners of WONCBP participants must wear a condom to protect against the transfer of study intervention through bodily fluids during the treatment period and for at least 105 days after the last dose of study intervention. Male participants: Male participants must inform their female sexual partners who are WOCBP of the contraceptive requirements of the protocol and are expected to adhere to using contraception with their partner. Male participants with female sexual partners who are WOCBP must agree to remain abstinent (complete avoidance of heterosexual intercourse) or use adequate contraceptive methods, defined as use of a condom by the male partner combined with use of a highly effective method of contraception by the female partner, during the treatment period and for at least 165 days after the last dose of study intervention. Male participants must not donate sperm for at least 165 days after the last dose of study intervention. Male participants with potentially postmenopausal partners who are under the age of 55 years must use condoms unless their partner's postmenopausal status has been confirmed by FSH level. Male participants in same-sex relationships or in relationships with WONCBP must agree to remain abstinent (complete avoidance of intercourse) or use a condom to prevent exposure of the partner to study intervention through ejaculate/seminal fluid during the treatment period and for at least 165 days after the last dose of study intervention. Eligibility Criteria for Part 2 Subjects with Systemic Amyloidosis Subjects with systemic amyloidosis are eligible to be included in the study only if all the following criteria apply: Understands the study procedures and can give signed informed consent Male or female ≥18 and ≤80 years of age. Mini Mental Status Exam (MMSE) score >27 (subjects >55 years of age only). Has a confirmed diagnosis of AL, ATTR, or other form of systemic amyloidosis, based on any one of the following: A histologic confirmation with a biopsy containing deposits of apple-green birefringent, Congophilic material or other amyloid staining (i.e., thioflavin T or sulfated alcian blue) with confirmatory immunohistochemistry, mass spectrometry or identification of an amyloidogenic genetic variant; Genetic screening with presence of amyloid-related pathology; or Amyloid-specific imaging study (e.g., bone scintigraphy and echocardiogram/CMR consistent with ATTR cardiac amyloid). Subjects with AL systemic amyloidosis must have achieved a hematologic very good partial response (VGPR) or complete response (CR) based on their most recent assessment (e.g., difference in free light chains <40 mg/L) and within 12 months of Screening and may be receiving maintenance daratumumab. Subjects with ATTR systemic amyloidosis may be receiving a TTR silencer (e.g., inotersen, vutrisiran, or patisiran) or a stabilizer (e.g., tafamadis or diflunisal), but not both. Women of childbearing potential (WOCBP): WOCBP must have a negative serum or urine pregnancy test within 24 hours prior to the start of study treatment. Must not be breastfeeding, lactating, or planning a pregnancy during the study period. WOCBP who are not exclusively in same-sex relationships must agree to remain abstinent (complete avoidance of heterosexual intercourse) or use adequate contraceptive methods, defined as use of a condom by the male partner combined with use of a highly effective method of contraception by the female partner, during the treatment period and for at least 105 days after the last dose of study intervention. Women of non-childbearing potential (WONCBP), and female participants with vasectomized male partners: WONCBP must agree to remain abstinent (complete avoidance of intercourse) or the male partners of WONCBP participants must wear a condom to protect against the transfer of study intervention through bodily fluids during the treatment period and for at least 105 days after the last dose of study intervention. Postmenopausal females must have a documented serum FSH level >40 mIU/mL at Screening to confirm menopause. Male participants: Male participants must inform their female sexual partners who are WOCBP of the contraceptive requirements of the protocol and are expected to adhere to using contraception with their partner. Male participants with female sexual partners who are WOCBP must agree to remain abstinent (complete avoidance of heterosexual intercourse) or use adequate contraceptive methods, defined as use of a condom by the male partner combined with use of a highly effective method of contraception by the female partner, during the treatment period and for at least 165 days after the last dose of study intervention. Male participants must not donate sperm for at least 165 days after the last dose of study intervention. Male participants in same-sex relationships or in relationships with WONCBP, must agree to remain abstinent (complete avoidance of intercourse) or use a condom to prevent exposure of the partner to study intervention through ejaculate/seminal fluid during the treatment period and for at least 165 days after the last dose of study intervention. Eligibility Criteria for Part 3 Subjects with Systemic Amyloidosis Subjects with systemic amyloidosis are eligible to be included in the study only if all the following criteria apply: Understands the study procedures and can give signed informed consent. Male or female ≥18 and ≤85 years of age. Has a confirmed diagnosis of ATTR cardiomyopathy (ATTR-CM), AL, or other form of systemic amyloidosis Imaging evidence of organ amyloid deposits. For ATTR cardiomyopathy subjects, genetic testing confirming wild type ATTR or identification of an amyloidogenic genetic variant is required. If genetic testing has not been performed prior to screening, then the test may be ordered during screening Subjects with ATTR cardiomyopathy may be receiving a TTR silencer (e.g., inotersen, vutrisiran, or patisiran) or a stabilizer (e.g., tafamadis or diflunisal), but not both. Subjects with AL systemic amyloidosis may be receiving maintenance daratumumab and must have Achieved a hematologic very good partial response (VGPR) or complete response (CR) based on their most recent assessment (e.g., difference in free light chains <40 mg/L) within 12 months of Screening or Achieved a partial hematologic response, is in stable condition (defined as >6 months without clonal or amyloidotic organ progression), is not receiving plasma cell directed (PCD) therapy and is not expected to require PCD therapy for the duration of the study. Women of childbearing potential (WOCBP): WOCBP must have a negative serum or urine pregnancy test within 24 hours prior to the start of study treatment. Must not be breastfeeding, lactating, or planning a pregnancy during the study period. WOCBP who are not exclusively in same-sex relationships must agree to remain abstinent (complete avoidance of heterosexual intercourse) or use adequate contraceptive methods, defined as use of a condom by the male partner combined with use of a highly effective method of contraception by the female partner, during the treatment period and for at least 105 days after the last dose of study intervention. Women of non-childbearing potential (WONCBP), and female participants with vasectomized male partners: WONCBP must agree to remain abstinent (complete avoidance of intercourse) or the male partners of WONCBP participants must wear a condom to protect against the transfer of study intervention through bodily fluids during the treatment period and for at least 105 days after the last dose of study intervention. Postmenopausal females must have a documented serum FSH level >40 mIU/mL at Screening to confirm menopause. Male participants: Male participants must inform their female sexual partners who are WOCBP of the contraceptive requirements of the protocol and are expected to adhere to using contraception with their partner. Male participants with female sexual partners who are WOCBP must agree to remain abstinent (complete avoidance of heterosexual intercourse) or use adequate contraceptive methods, defined as use of a condom by the male partner combined with use of a highly effective method of contraception by the female partner, during the treatment period and for at least 165 days after the last dose of study intervention. Male participants must not donate sperm for at least 165 days after the last dose of study intervention. Male participants in same-sex relationships or in relationships with WONCBP must agree to remain abstinent (complete avoidance of intercourse) or use a condom to prevent exposure of the partner to study intervention through ejaculate/seminal fluid during the treatment period and for at least 165 days after the last dose of study intervention.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Scott Stephens, RN
Phone
3212287400
Email
Sstephens@attralus.com
Facility Information:
Facility Name
Q-Pharm Pty Ltd
City
Herston
State/Province
Queensland
ZIP/Postal Code
4006
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Richard Friend
Facility Name
Princess Alexandra Hospital
City
Woolloongabba
State/Province
Queensland
ZIP/Postal Code
4102
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Dariusz Korczyk, Dr
Facility Name
Flinders Medical Centre
City
Bedford Park
State/Province
South Australia
ZIP/Postal Code
5042
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Joseph Selvanayagam
Facility Name
Box Hill Hospital
City
Box Hill
State/Province
Victoria
ZIP/Postal Code
3128
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Simon Gibbs
Facility Name
Royal Perth Hospital
City
Perth
State/Province
Western Australia
ZIP/Postal Code
6000
Country
Australia
Individual Site Status
Active, not recruiting

12. IPD Sharing Statement

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Study of AT-02 in Healthy Volunteers and Subjects With Systemic Amyloidosis

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